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MSCs may have a delayed effect in reducing airway inflammation, airway hyper-responsiveness and remodeling in experimentally induced asthmatic cats. Results warrant additional investigation of MSC therapy for asthma in cats.

Background Mesenchymal stem cells (MSCs) decrease airway eosinophilia, airway hyperresponsiveness (AHR), and remodeling in murine models of acutely induced asthma. We hypothesized that MSCs would diminish these hallmark features in a chronic feline asthma model. Objective To document effects of allogeneic, adipose-derived MSCs on airway inflammation, airway hyperresponsiveness (AHR), and remodeling over time and investigate mechanisms by which MSCs alter local and systemic immunologic responses in chronic experimental feline allergic asthma. Methods Cats with chronic, experimentally-induced asthma received six intravenous infusions of MSCs (0.36–2.5X10E7 MSCs/infusion) or placebo bimonthly at the time of study enrollment. Cats were evaluated at baseline and longitudinally for one year. Outcome measures included: bronchoalveolar lavage fluid cytology to assess airway eosinophilia; pulmonary mechanics and clinical scoring to assess AHR; and thoracic computed tomographic (CT) scans to assess structural changes (airway remodeling). CT scans were evaluated using a scoring system for lung attenuation (LA) and bronchial wall thickening (BWT). To assess mechanisms of MSC action, immunologic assays including allergen-specific IgE, cellular IL-10 production, and allergen-specific lymphocyte proliferation were performed. Results There were no differences between treatment groups or over time with respect to airway eosinophilia or AHR. However, significantly lower LA and BWT scores were noted in CT images of MSC-treated animals compared to placebo-treated cats at month 8 of the study (LA p=0.0311; BWT p=0.0489). No differences were noted between groups in the immunologic assays. Conclusions and Clinical Relevance When administered after development of chronic allergic feline asthma, MSCs failed to reduce airway inflammation and AHR. However, repeated administration of MSCs at the start of study did reduce computed tomographic measures of airway remodeling by month 8, though the effect was not sustained at month 12. Further study of MSC therapy including repeated MSC administration is warranted to assess impact on remodeling in chronic asthma.

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A 7-year-old female spayed Bulldog was presented to the University of Missouri Veterinary Medical Teaching Hospital for a 2-month history of progressive abdominal distension that was unresponsive to treatment for presumptive cardiac disease. On presentation, the dog was quiet, alert, and responsive. The vital parameters, including temperature, and heart and respiratory rates, were within normal limits. Physical examination revealed severe abdominal distention, symmetrical alopecia along the tail and dorsum, markedly enlarged mammary glands and vulva, and mucoid red-brown vulvar discharge. CBC and chemistry data revealed only mild abnormalities including mature neutrophilia, minimally regenerative anemia, hypoalbuminemia, and hyperglobulinemia. Thoracic radiographs revealed several soft tissue opacities in the lungs suggestive of metastatic disease. Therapeutic abdominocentesis was performed and approximately 1.5 L of serosanguinous fluid was removed. This fluid was submitted for evaluation and was classified as a modified transudate (2828 cells/lL, total protein 3.3 g/dL) with mild suppurative inflammation and moderate numbers of round, mildly pleomorphic cells most consistent with reactive mesothelial cells. An abdominal ultrasound examination revealed a multilobulated central abdominal mass that was too large to be measured. The organ of origin was not apparent. Fine-needle aspirates of the mass were submitted for cytologic evaluation (Figure 1). Figure 1. Aspirates of an intra-abdominal mass in a 7-year-old female spayed dog. Wright-Giemsa (A)920 objective. (B) 9100 objective. A B